Abstract
Cathepsin L (ctsl), a lysosomal cyteine protease over expressed and secreted by cancer cells, has been implicated in a number of physiological and pathological processes including tumor cell proliferation and metastasis. In the present study we demonstrate that an unknown mRNA of human origin (Gene Bank accession number AF 217997) is a splice variant of human cathepsin L mRNA (hCATL A IV) and encodes a truncated form of cathepsin L (Δctsl) containing only 151 C-terminal amino acids. This isoform is cytotoxic to the mammalian cells. Transient transfection studies revealed that unlike ctsl, upon over expression in eukaryotic cells Δctsl is not secreted in to the media. Immunogold electron microscopy revealed its localization to nuclear, perinuclear and cytosolic regions. In view of its cytotoxic property, targeted expression of Δctsl in tumor cells may prove useful in the management of cancer.
Keywords: Splice variant, transfection, immunogold electron microscopy, cancer
Protein & Peptide Letters
Title: Truncated Human Cathepsin L, Encoded by a Novel Splice Variant, Exhibits Altered Subcellular Localization and Cytotoxicity
Volume: 17 Issue: 2
Author(s): Poonam Sansanwal, Abhay A. Shukla, Taposh K. Das and Shyam S. Chauhan
Affiliation:
Keywords: Splice variant, transfection, immunogold electron microscopy, cancer
Abstract: Cathepsin L (ctsl), a lysosomal cyteine protease over expressed and secreted by cancer cells, has been implicated in a number of physiological and pathological processes including tumor cell proliferation and metastasis. In the present study we demonstrate that an unknown mRNA of human origin (Gene Bank accession number AF 217997) is a splice variant of human cathepsin L mRNA (hCATL A IV) and encodes a truncated form of cathepsin L (Δctsl) containing only 151 C-terminal amino acids. This isoform is cytotoxic to the mammalian cells. Transient transfection studies revealed that unlike ctsl, upon over expression in eukaryotic cells Δctsl is not secreted in to the media. Immunogold electron microscopy revealed its localization to nuclear, perinuclear and cytosolic regions. In view of its cytotoxic property, targeted expression of Δctsl in tumor cells may prove useful in the management of cancer.
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Cite this article as:
Sansanwal Poonam, Shukla A. Abhay, Das K. Taposh and Chauhan S. Shyam, Truncated Human Cathepsin L, Encoded by a Novel Splice Variant, Exhibits Altered Subcellular Localization and Cytotoxicity, Protein & Peptide Letters 2010; 17 (2) . https://dx.doi.org/10.2174/092986610790225932
DOI https://dx.doi.org/10.2174/092986610790225932 |
Print ISSN 0929-8665 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5305 |
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Plants are still the major repository of biologically active substances. In the last two decades, however, natural peptides and proteins of plant origin have gained increasing attention due to their pharmacological activities over a variety of human illnesses, including those mediated by infections and parasitosis and those involving different cellular ...read more
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